The inflammatory response characterized by red, swelling, heat, pain and dysfunction, is a protective response of the body against external injury. Appropriate inflammatory response is required for protecting hosts from external insults, thus keeping tissue homeostasis. However, the excessive or prolonged inflammation leads to tissue damage and organ dysfunction, such as pneumonia, hepatitis, nephritis, arthritis, etc. Usually, the process of inflammation includes local tissue injury, oozy and tissue hyperplasia. The skin, as the first line of host defense, interfaces with the environment and is exposed to a myriad of microorganisms. Thereby, skin inflammation is usually triggered by external stimulus, including inflammation of psoriasis, atopic dermatitis, neurodermatitis, etc. The etiology of these types of skin diseases is very complex and these diseases are hardly to be cured. Even though these diseases are cured, they are easily recurred.
Lipopeptides consist of a hydrophilic peptide chain and a lipophilicaliphatic chain, that is, about 10 peptides and aliphatic chain form a circular or linear lipopeptide. Lipopeptides are generally produced by Gram-positive bacteria and exhibit a variety of biological activities. Accumulating evidence shows that lipopeptides can function as surfactants, fungicides or insecticides. Moreover, it has been reported that a subclass of acylated lipopeptides have anti-inflammatory function (Long. E M, et al. A subclass of acylated anti-inflammaroty mediators usurp Toll-like receptor 2 to inhibit neutrophil recruitment through peroxisome proliferator activated receptor gamma. PNAS, 2011, 108(39):16357-62). However, beside the above lipopeptides, no other lipopeptide with anti-inflammatory activity has been identified. Therefore, it will be a promising field of bio-pharmacy.
Staphylococcus epidermidis, as one of most common commensal bacterial species, normally resides on the surface of the skin. Staphylococcus epidermidis produces many kinds of antibacterial molecules, including Pep5, PSMs, etc. All these peptides have anti-microbial activity. Besides antibacterial molecules, lipoteichoic acid (LTA), a product of staphylococci, has shown an anti-inflammatory effect on inhibiting TLR3-dependent inflammation after skin injury (LaiY, et al. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat Med. 2009, 15(12):1377-82.). However, whether lipopeptides produced by Staphylococcus epidermal have the anti-inflammatory activity remains unknown.
The present invention provides a novel anti-inflammatory lipopeptide which can suppress the inflammatory responses induced by poly(I:C), prevent the inflammation in wounds after skin injury, and alleviate inflammatory responses of skin inflammatory diseases such as allergic dermatitis.